In vitro Comparative Degradation Study of Different Brands of Domperidone Using UV Spectrophotometer

Transcription

1 British Journal of Research Original Article In vitro Comparative Degradation Study of Different Brands of Domperidone Using UV Spectrophotometer Md. Jakaria*, Abul Hasanat and Md Ibrahim Tarek Department of Pharmacy, International Islamic University Chittagong (IIUC), Chawkbazar, Chittagong-4203, Bangladesh *Corresponding author A B S T R A C T Objective: The aim of the study was to perform forced degradation studies of the different brands of Domperidone 10 mg. Methods: This drug was subjected to different stress conditions as per International Conference on Harmonization guidelines (ICH). An ultraviolet UV spectroscopic method was developed for analysis of the drug in the presence of the degradation products. Distilled water was used as a solvents. The amount of degraded drugs was calculated by taking the absorbance at 287 nm. Results: According to the assay limit of USP specified that the content should not be less than 95% and not more than 105% of labelled amount. All brands were degraded by after the heat exposure. On addition of basic ph and acidic ph, all brands were also degraded. Conclusion: It was concluded that all brands degraded from ranges for all the stresses applied for degradation studies. Keywords: Domperidone 10 mg, D 2 receptor, Degradation studies, Assay. INTRODUCTION Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product. The FDA and ICH guidance s state the requirement of stability testing data to understand how the quality of a drug substance and drug product changes with time under the influence of various environmental factors Knowledge of the stability of molecule helps in selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for regulatory documentation. Forced degradation is a process that involves degradation of drug products and drug substances at conditions more severe than accelerated conditions and thus generates degradation products that can be studied to determine the stability of the molecule. The ICH guideline states that stress testing is intended to identify the likely degradation products which further British Journal of Research

2 helps in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the stability indicating procedures used 1. Domperidone (DOM), chemically known as 5-Chloro-1-{1-[3-(2-oxo-2, 3- dihydro-1h-benzimidazol-1-yl) propyl]-4- piperidinyl}-1, 3-dihydro-2H-benzimidazol- 2-one (Figure 1) 2. It is a selective D 2 receptor antagonist, the D 2 Receptors in the CTZ (Chemo Trigger Zone) and causes prolactin release from the anterior pituitary. It is official in British Pharmacopoea and European Pharmacopoea 3-5. It speeds gastrointestinal peristalsis, and is used as antiemetic for nausea or vomiting associated with gastrointestinal disorders e.g., dyspepsia, heartburn, epigastric pain and with cytotoxic and other drug treatments. It does not enter the CNS (Blood Brain Barrier) to a significant extent. Side effects include galactorrhea, gynecomastia, or menstrual irregularities and it may be 91%- 93% binds with protein 6,7. Literature review reveals that some of the UV, HPLC methods have been reported for the simultaneous estimation of Domperidone 5,8-14. The aim of the study was to perform forced degradation studies of the different brands of domperidone under hydrolytic (acidic and basic), and thermal stress conditions, defined under ICH guideline by using spectrophotometer. These types of degradation studies of drugs and these are very helpful for health care professionals METHODS Reagents Analytical grade reagents were used 1N sodium hydroxide, 1N hydrochloric acid, de-mineralized water and distilled water. Wavelength Selection About 100 ppm of domperidone was accurately prepared in distill water. The wavelength maxima (λmax) was observed at 287 nm and this wavelength was adopted for absorbance measurement. Standard Stock Solution The seven different brands were purchased from a local medicine shop located in Bayzid Bostami, Chittagong. All tablets of brand have the same batch number and were labeled to contain domperidone 10 mg per tablet. All the seven brands have 3 year shelf life. Weigh and finally crushed tablets accurately for making primary solutions of domperdone 10 mg, Motigut ( gm) Square pharmaceuticals, Domilux ( gm) Popular pharmaceutical, Dysnov ( gm) Unimed & Unihealth, Dominol ( gm) Whitehorse pharma, Domar ( gm) Pacific pharmaceuticals, Perion ( gm) Globe Pharmaceutical, Doperon ( gm) United chemicals & pharmaceuticals were weighed accurately and introduced in 100 ml volumetric flasks. Distill water was added and shaken vigorously and make up the volume up to 100 ml to make the strength of the solution 100ppm in 100 ml. For Acid To study the effect of acid, 5 ml of 100 ppm solution of each brand was taken in seven separated test tubes then 5ml of 1N HCl was added in each test tube. They were then left for a period of 60 minutes. Upon completion of time period, solutions were transferred to acuvette separately and then absorbance of the solutions was recorded at the wavelength of 287 nm. For Base To study the effect of acid, 5 ml of 100 ppm solution of each brand was taken in seven separated test tubes then 5 ml of 1N

3 NaOH was added in each test tube. The samples were then left for a period of 60 minutes. Upon completion of time period, solutions were transferred to a cuvette separately and then absorbance of the solutions was recorded at the wavelength of 287 nm. For Heat To study the effect of heat, 5 ml of 100 ppm solution of each brand was taken in seven separated test tubes each containing 5 ml of water, than place these solutions in water bath for 60 min and absorbance of the solutions was recorded at the wavelength of 287 nm. RESULTS AND DISCUSSION This research was performed with the purpose to compare the degree of degradation in seven different brands of domperidone 10 mg. Table 1 shows the variation in absorbance after the effect of different degradation parameters. The limit of assay by USP specified that the content should not be less than 95% and not more than 105% of labeled amount. All brands were degraded in acidic and basic ph (table 2, 3) showing that ph alteration has the most degradation impact on these products. All brands was also degraded after the heat exposure (table 4). CONCLUSIONS It was used to study the stressdegradation studies as per ICH guidelines. Domperidone was found to be degraded in almost all types of stress conditions and was found to be less stable. The method was used is accurate and precise as well as reproducible and economical and can be successfully used degradation studies of different dosage form. It was concluded that all brands degraded from ranges for all the stresses applied for degradation studies. ACKNOWLEDGEMENT The authors greatly acknowledge to Dr. Safila Naveed, Associate Professor, Faculty of Pharmacy, Jinnah University for Women, Karachi, Pakistan for her helpful information and suggestions during the period of laboratory work. REFERENCES 1. Blessy M, Patel RD, Prajapati PN, Agrawal YK. Development of forced degradation and stability indicating studies of drugs. Review Paper. Journal of Pharma Analysis 2014; 4(3): Chemspider, Domperidone, www. chemspider.com/chemical-structure html, date accessed on 05/11/ European Pharmacopoeia. 3 rd edition, Council of Europe Strasburg 1997: British Pharmacopoeia, HMSO Publication, London; 1(2002); Through CD-ROM. 5. Patel AH, Patel JK, Patel KN. Development and validation of derivative spectrophotometric method for simultaneous estimation of domperidone and rabeprazole sodium in bulk dosage forms. Int. J. Ph. Sci 2010; 2(1): Bennett and Brown, Clinical Pharmacology. 10 th Edition, Churchill Livingstone, New York, U.S.A., 2008: Pubchem, Domperidone, pubchem.ncbi.nlm.nih.gov/compound/do mperidone#section=top, date accessed on 05/11/ Sivakumar T, Manavalan R, and Valliappan K. Development and validation of a reversed-phase HPLC method for simultaneous determination of domperidone and pantoprazole in

4 pharmaceutical dosage forms. Acta chromatographica 2007; 18: Chitlange SS, Mulla AI, Pawbake GR and Wankhede SB. Simultaneous Spectrophotometric Estimation Of Dexrabeprazole And Domperidone In Capsule Dosage Form. International Journal of Pharmaceutical Quality Assurance 2010; 2: Tarkase KN, Tarkase MK, Dokhe MD and Wagh VS. Development And Validation of Spectrophotometric Method For Simultaneous Estimation of Cinnarizine And Domperidone Maleate In Pure And Tablet Dosage Form. Indian Journal of Pharmaceutical Sciences 2012; 3: Kulkarni AS, Balkrishna MV. Method Development and Validation for the Simultaneous Determination of Omeprazole and Domperidone in Solid Dosage form by Rp-Hplc. Indian Journal of Pharmacy and Pharmaceutical Sciences 2012; 4: Babar SJ, Mane VB, Boise DSB. Development and Validation of UV- Spectrophotometric Methods for Simultaneous Estimation of Paracetamol and Domperidone in Bulk and Tablet Dosage Form. Indian Journal of Pharmacy and Pharmaceutical Sciences 2012; 4: Pardeep K, Sarma GS, Vika P. Development and Validation of Derivative Spectrophotometric Method For Simultaneous Estimation Of Domperidone and Esomeprazole. International Journal of Universal Pharmacy and Life Sciences 2011; 1: Baldha RG, Vandana PB, and Bapna M. Simultaneous Spectrophotometric Estimation of Rabeprazole Sodium And Domperidone In Combined Dosage Forms. International Journal of Pharm Tech Research 2010; 2: Naveed S, Waheed N and Nazeer S. Degradation studies of ampicillin in API and formulations. J App Pharm 2014; 6(3): Naveed S, Naseem Y, Samie S, Khan S, Siddiqui S, Bushra and Ramzan S. Degradation Study of Five Different Brands of Ciprofloxacin Using UV- Visible Spectrophotometer and Their Comparitive study. International Research Journal of Pharmacy 2014; 5(3): Naveed S, Shafiq A, Khan M, Jamal M, Zafar H, et al. Degradation Study of Available Brands of Metformin Karachi Using UV Spectrophotometer. J. Diabetes Metabolism 2014; 5: Naveed S*, Nazeer S and Waheed N. Degradation study of Meloxicam by UV-spectroscopy. British Journal of Research 2014; 1(3):

5 S. No. Table 1. Showing absorbance of drug in different parameters Brand name of standard after acidic ph effect after basic ph effect after heat effect 1. Motigut Domilux Dysnov Dominol Domar Perion Doperon Table 2. Showing effect of acid S. No. Brands % Assay 1. Motigut 52.59% 2. Domilux 57.12% 3. Dysnov 65.45% 4. Dominol 59.56% 5. Domar 47.54% 6. Perion 40.89% 7. Doperon 51.29% Table 3. Showing effect of base S. No. Brands % Assay 1. Motigut 64.24% 2. Domilux 67.14% 3. Dysnov 75.34% 4. Dominol 75.80% 5. Domar 61.76% 6. Perion 50.66% 7. Doperon 61.07% Table 4. Showing effect of heat S. No. Brands % Assay 1. Motigut 48.79% 2. Domilux 46.84% 3. Dysnov 48.18% 4. Dominol 51.61% 5. Domar 40.82% 6. Perion 33.23% 7. Doperon 31.74%

6 Figure 1. Domperidone structure